The NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respira
tory chain is by ar the most complicated of the proton-translocating enzyme
s involved in the oxidative phosphorylation. Many clues regarding both elec
tron transfer and proton translocation are still unknown. In this sense, in
hibitor assays are relevant and useful pieces for elaborating a suitable mo
del to explain the elusive bioenergetic mechanism of this enzyme. This shor
t review presents the most recent advances in inhibitor studies and highlig
hts the major controversies.